Anouk M M Vaes1, Michael Tieland2, Margot F de Regt2, Jonas Wittwer3, Luc J C van Loon4, Lisette C P G M de Groot2. 1. Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. Electronic address: anouk.vaes@wur.nl. 2. Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. 3. DSM Nutritional Products Ltd., R&D Human Nutrition and Health, P.O. Box 2676, CH-4002 Basel, Switzerland. 4. Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Abstract
BACKGROUND & AIMS:Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L. METHODS: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D3, 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. RESULTS: Supplementation with 20 μg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and 1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. CONCLUSIONS: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D3 concentrations to be maintained between 75 and 100 nmol/L. TRIAL REGISTRATION NUMBER: NCT01868945.
RCT Entities:
BACKGROUND & AIMS: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L. METHODS: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D3,25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. RESULTS: Supplementation with 20 μg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and 1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. CONCLUSIONS: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D3 concentrations to be maintained between 75 and 100 nmol/L. TRIAL REGISTRATION NUMBER: NCT01868945.
Authors: Dominique Turck; Jacqueline Castenmiller; Stefaan De Henauw; Karen Ildico Hirsch-Ernst; John Kearney; Alexandre Maciuk; Inge Mangelsdorf; Harry J McArdle; Androniki Naska; Carmen Peláez; Kristina Pentieva; Alfonso Siani; Frank Thies; Sophia Tsabouri; Marco Vinceti; Francesco Cubadda; Thomas Frenzel; Marina Heinonen; Rosangela Marchelli; Monika Neuhauser-Berthold; Morten Poulsen; Miguel Prieto Maradona; Josef Rudolf Schlatter; Henk van Loveren; Céline Dumas; Ruth Roldán-Torres; Hans Steinkellner; Helle Katrine Knutsen Journal: EFSA J Date: 2021-07-01